Involvement of T-complex protein-1δ in dopamine triggered apoptosis in chick embryo sympathetic neurons

R. Zilkha-Falb, A. Barzilai, R. Djaldeti, I. Ziv, E. Melamed, A. Shirvan

Research output: Contribution to journalArticlepeer-review

Abstract

The neurotransmitter dopamine (DA) is capable of inducing apoptosis in post-mitotic sympathetic neurons via its oxidative metabolites. The differential display method was applied to cultured sympathetic neurons in an effort to detect genes whose expression is transcriptionally regulated during the early stages of DA-triggered apoptosis. One of the up-regulated genes was identified as the chick homologue to T-complex polypeptide-1δ (TCP-1δ), a member of the molecular chaperone family of proteins. Each chaperone protein is a complex of seven to nine different subunits. A full-length clone of 1.9 kilobases was isolated containing an open reading frame of 536 amino acids with a predicted molecular weight of 57,736. Comparison with the mouse TCP-1δ revealed 78 and 91% homology on the DNA and protein levels, respectively. Northern blot analysis disclosed a steady and significant increase in mRNA levels of TCP-1δ after DA administration, reaching a peak between 4 and 9 h and declining thereafter. Induction of the TCP-1δ protein levels was also observed as a function of DA treatment. Overexpression of TCP-1δ in sympathetic neurons accelerated DA-induced apoptosis; inhibition of TCP-1δ expression in these neurons using antisense technology significantly reduced DA-induced neuronal death. These findings suggest a functional role for TCP-1δ as a positive mediator of DA-induced neuronal apoptosis.

Original languageEnglish
Pages (from-to)36380-36387
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number46
DOIs
StatePublished - 17 Nov 2000

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